The overall goal of this research is to understand how local networks of binocular cells in the visual cortex combine inputs from the left and right eyes. Understanding binocular vision at the local network level may contribute to the development of new forms of rehabilitation for restoring function to the compromised visual cortex in strabismus, amblyopia, or physical damage to the eye. The dominant approach for assaying the binocular properties of cortical neurons employs monocular tests of ocular dominance to infer binocular function. However, the relationship between ocular dominance and binocular disparity-a property that is critical for stereopsis and can only be assessed with simultaneous stimulation of both eyes-remains unclear. The functional micro-architecture of disparity tuning has never been described in any species. Furthermore, while great strides have been made in identifying the physiological and biochemical changes that result from monocular deprivation, there are clear inter-species differences (and variability amongst different studies in the same species) when ocular dominance is the only assay used to determine the binocular properties of cortical neurons. By using the new technique of two-photon calcium imaging in vivo, the specific goals of this proposal are to determine how these distinct binocular properties are mapped in cortical circuits, to assess whether there are systematic relationships between the mapping of ocular dominance and disparity tuning, and to evaluate how these properties are impacted by monocular deprivation. In Aim 1, we will resolve whether there is local mixing of neurons from different ocular dominance groups or whether these maps are as precise and smooth as those found for orientation selectivity. In Aim 2, we determine whether a micro-architecture for binocular disparity exists and whether ocular dominance can predict disparity tuning. In Aim 3, we examine whether monocular deprivation during the critical period disrupts the micro-architecture of binocular disparity. Clustering of cells that retain normal disparity tuning after monocular deprivation may provide important clues into the local circuit mechanisms that drive cortical neurons to become disparity selective. In Aim 4, we examine whether the single-cell fluorescence changes obtained with calcium imaging of neuronal cell bodies correlate with the single-cell firing rates obtained with electrophysiological methods. These results promise to shed new light on the functional organization of cortical circuits that mediate binocular vision, and the detrimental effects of altered visual experience.